Multicomponent meso thread containing hyaluronic acid and method for producing same (variants)

ABSTRACT

The group of inventions relates to the field of aesthetic, plastic and reconstructive cosmetology/medicine, and more particularly to meso threads used for remedying aesthetic and age-related changes to the skin, and to methods for producing such threads. Proposed is a multicomponent meso thread consisting of a core and a shell. The core is realized in the form of a fibroin thread, and the shell contains hyaluronic acid or a salt thereof or a polyelectrolyte complex of hyaluronic acid or a salt thereof and chitosan or a salt thereof. Also proposed are a variant of the thread having a plastifying agent in the shell, and methods for producing the proposed meso threads.

CROSS-REFERENCE TO RELATED APPLICATIONS

The instant application is a continuation application of U.S. Ser. No.15/554,078 filed on Aug. 28, 2017 which is a National Phase Entry ofInternational Patent Application No. PCT/RU2016/000208, filed on Apr.11, 2016, and claims priority to Russian Patent Application No.2015116096, filed on Apr. 28, 2015, the entire specifications of both ofwhich are expressly incorporated herein by reference.

FIELD OF THE INVENTION

The group of inventions belongs to the field of aesthetic, plastic andreconstructive cosmetology/medicine, to-wit, the mesotherapeutic threadsused to correct aesthetic and age-related skin changes, as well as theways to manufacture them.

BACKGROUND OF THE INVENTION

Today, one of the directions in the industry of materials forcosmetology and plastic surgery are the development and production ofmesotherapeutic threads (microthreads, 3D threads), the cosmetologicalthreads used to perform the minimally invasive technique ofthreadlifting. The method consists in the subcutaneous injection ofmesothreads in order to reinforce facial tissues and eliminate ptosis bymeans of biodegradable mesothreads that allow for modelling tissues inany areas including face and body parts that are not treatable usingother technologies. A mesothread is a thread used to perform 3Dmodelling of face and body contours and to connect tissues to form ascar, or epithelization. Mesothreads can even out the skin relief thanksto the compressing activity of threads introduced subcutaneously. Anessential condition for the bioreinforcement to have clinical effect isthe creation of stringers that ensure pronounced and long-lastinglifting of the soft tissues.

Mesothreads are made using threads with a monofilament structure, highbiocompatibility, optimum physical and mechanical properties(durability, stiffness, strain characteristics, thread's “memoryeffect”) and resistance to infection. After having performed theirfunctions and formed a normal durable scar, the mesothreads shouldcompletely degrade, their degradation products being included into thebody's metabolism without negatively affecting it. In other words, thethread lifting procedure should be reversible (maintaining the effectfor a period between 0.5 and 2 years) and compatible with other anti-ageprocedures.

At present, there are various mesothreads made from different materials.Aesthetic therapy uses skin lifting using golden threads (e.g., patentKR 1020140071885, Dec. 6, 2014). This method is efficient but still hasits drawbacks. The golden threads do not biodegrade and can causeallergies because they contain metals; patients who have had their skinlifted using golden threads are not allowed to undergo most instrumentalphysiotherapeutic procedures and plastic surgeries anymore.

The most suitable material for making mesothreads are biodegradablepolymers. One of the most widely used among them is now polydioxanone(PDO). Threads made from it have outstanding biocompatibility anddegrade within 8 month, are elastic, do not produce a “saw” effect andare atraumatic.

At the technical level, the RF patent No. 2524610, published in 2014(prototype), describing a multi-component mesothread consisting of apolydioxanone core and a coat made from polyglycolic acid, used tocorrect aesthetic and age-related skin changes.

Following are the drawbacks of PDO-based mesothreads: such threads fullydegrade in the human organism by means of hydrolysis within 4-8 months;the intermediate hydrolysis products accumulate in the organism next tothe areas where the mesothreads are injected. Since the hydrolysisproducts of PDO-based mesothreads have acidic nature, they cause a localdecrease in the pH level of the environment and, therefore, a moderate(low to average) tissue reaction. So far, there is no way to avoid it,since PDO degrades through water hydrolysis only, where acidicenvironment triggers the autocatalytic effect that accelerates furtherdegradation of PDO. Studies show that PDO suppresses the adhesion ofmacrophages to some extent and causes the effect of localimmunosuppression in the implantation area: there is a decrease in boththe levels of humoral and cell immunity, mostly NK lymphocytes. Thedecreased amount of NK lymphocytes results in the development ofoncological diseases and aggravations in the course of viral infections.

SUMMARY OF THE INVENTION

The current invention group purports to create strong mesothreads madefrom natural polymers, biocompatible with body tissues and degradingwithin 0.5-2 years, depending on the thickness of the coating.

The technical result consists in the creation of mesothreads that arebetter biocompatible with human tissues and thereby ensure that thereare no tissue reactions, risk of infiltration, allergies, or hematomas.

To handle this issue and ensure the technical result, a multi-componentmesothread is proposed, consisting of a core and coating. The core is athread (filaments) made from fibroin, and the coating containshyaluronic acid (HA) or its salt, or a polyelectrolyte complex (PEC) ofhyaluronic acid or its salt with chitosan or its salt.

One of the following salts of hyaluronic acid may be used:tetraalkylammonium, lithium, sodium, potassium, calcium, magnesium,barium, zinc, aluminum, copper, aurate or mixed salt, and hydrosalt ofhyaluronic acid.

As chitosan, it is suggested to use chitosan with over 50% deacetylationdegree. As chitosan salt, we suggest using chitosan acetate, chisotanchloride, or chitosan lactate.

The core and/or the coating may also contain plastifying agent. Theplastifying agent may be, in particular, polyvinyl alcohol.

The coating may additionally contain anti-infection and/or antisepticagent, and/or antibiotic. As the anti-infection agent,beta-(5-nitrofuril-2)-acrolein may be used. As the antiseptic,benzyldimethyl [3-(myristoylamino)propyl] ammonium chloride monohydrateis used.

The coating may additionally content a coupling (sealing) agent, beingone of the following: ethyleneglycol diglycidyl ether, diethyleneglycoldiglycidyl ether, triethyleneglycol diglycidyl ether, polyethyleneglycoldiglycidyl ether, propyleneglycol diglycidyl ether, 1,4-butanedioldiglycidyl ether, 1,6-hexandiol diglycidyl ether, genipin.

We also suggest a multi-component mesothread consisting of a core and acoating, the core being a fibroin thread and the coating containinghyaluronic acid or its salt or a polyelectrolyte complex of hyaluronicacid or its salt with chitosan or its salt, as well as polyvinyl alcoholas a plastifying agent.

We suggest a method to obtain a bicomponent mesothread consisting of acore being a fibroin thread and a coating containing hyaluronic acid orits salt. This method comprises, first, the preparation of a formingsolution of hyaluronic acid or its salt, previously swollen and solvedin water; after the solving, 10-40 mass % of ethyl alcohol areintroduced into the solution; the ready solution is kept for 22±2 hoursat the temperature of 22±2° C. up to complete readiness (until ripened)and deaeration. Then, the fibroin thread is drawn through a formingsolution of hyaluronic acid or its salt and the calibrated nozzle(spinneret), and dried.

We also suggest a method to obtain a multi-component mesothreadconsisting of a core being a fibroin thread and a coating containing apolyelectrolyte complex of hyaluronic acid or its salt with chitosan orits salt. This method comprehends that a forming solution of hyaluronicacid or its salt is first prepared as follows: hyaluronic acid or itssalt are previously swollen and solved in water; after the solving,10-40 mass % of ethyl alcohol are introduced into the solution; theready solution is kept for 22±2 hours at the temperature of 22±2° C. upto complete readiness and deaeration. Then, the forming solution ofchitosan or its salt is prepared as follows: chitosan or its salt arepreviously swollen in water, then mixed gradually with an amount ofconcentrated acetic acid equal to the contents of chitosan; after thechitosan is solved, 10-40 mass % of ethyl alcohol are introduced. Theready solution is kept for 22±2 hours at the temperature of 22±2° C. upto complete readiness. At the first stage, the fibroin thread is drawnthrough a forming solution of hyaluronic acid or its salt and thecalibrated nozzle, and dried. At the second stage, the thread obtainedduring the first one is drawn through a forming solution of chitosan orits salt or a forming solution of hyaluronic acid or its salt, in such away that layers of hyaluronic acid or its salt went alternating withlayers of chitosan or its salt. Then, the thread is drawn through acalibrated nozzle and dried. The second stage is repeated n times.

The forming solution of hyaluronic acid and/or the forming solution ofchitosan is supplemented by the coupling agent (up to 10 mass % of theweight of the polymer), being one of the following: ethyleneglycoldiglycidyl ether, diethyleneglycol diglycidyl ether, triethyleneglycoldiglycidyl ether, polyethyleneglycol diglycidyl ether, propyleneglycoldiglycidyl ether, 1,4-butanediol diglycidyl ether, 1,6-hexandioldiglycidyl ether, glutaric aldehyde, genipin.

The forming solution of hyaluronic acid or the forming solution ofchitosan is supplemented by the coupling agent (polyvinyl alcohol).

DETAILED DESCRIPTION

The thread made from fibroin (preferably, silk fibroin) is highlyhygroscopic and adhesive to macromolecules of both chitosan andhyaluronic acid. As the fibroin thread, the surgical silk thread can beused, containing over 99% of fibroin, without coating.

Chitosan is a linear cationic polysaccharide with high biocompatibility,as well as antibacterial, wound-healing, haemostatic and antisepticproperties. In human body, chitosan is metabolized to D-glucosamin withlysozyme. Hyaluronic acid is a linear anionic polysaccharide, one of thecomponents of the extracellular matrix, with a high adsorbtion and waterretention capacity, and a significant role in the proliferation andmigration of cells.

Since polysaccharides have a very high cohesion energy level, almost allof them are non-fusible: their fusioning temperature is higher thantheir decomposition temperature. Polysaccharides may be processed intoproducts, including threads, only through solutions.

A technologically simple way of obtaining threads containing HA consistsin the treatment of fibrous materials with polymer (or polymercomposition) solutions and subsequent evaporation of the solvent. Thecoating hardens through evaporation of the solvent or the dispersivemedium, as well as through chemical reaction with the hardener or theprecipitator. It should be noted that the technological process isdetermined by the requirements applying to the ready threads as tomedical materials.

The presence of a chitosan macromolecule free amino group in eachelementary unit (a carboxylic group for hyaluronic acid) gives them theproperties of polyelectrolytes, polybases and polyacids, respectively.Therefore, when applied layer by layer, chitosan or its salt andhyaluronic acid or its salt form polyelectrolyte complexes (PECs) in theform of polyelectrolyte monolayers (PEMs). Each time a layer is applied,a small amount of polyelectrolyte is adsorbed and the superficial chargeis restored. This approach is a way to form polycation-polyanion layersin the form of electrostatically sealed films, in a gradual andcontrolled manner. The main benefit of threads with PEC coating is thatthere is no need to use additional coupling agents. Polyelectrolyticcomplexes of hyaluronic acid with chitosan are not water-soluble, and,within a living organism, they biodegrade slower than their separatecomponents.

The addition of polyvinyl alcohol (PVA) into the forming solutiondecreases its superficial tension and increases spinnability. Themesothread with PVA plastifying agent has a smoother surface, is highlyelastic and a longer time of biodegradation in the organism. Asplastifying agent, PVA with deacetylation degree over 99% and molecularweight of 5-100 kDa is used. The PVA aqueous solution is prepared inwater bath at a temperature of 88±2° C. After the PVA is fully solved,up to 20 mass % of ethyl alcohol are introduced into the solution. ThePVA is added in the form of a solution in such a way that the content ofPVA constitutes 0.1-20 mass % in relation to chitosan or hyaluronicacid.

The molecular weight of the hyaluronic acid used to make the mesothreadranks between 2 and 2,000 kDa.

The molecular weight of chitosan used to make the mesothread ranksbetween 1 and 1,000 kDa.

In some cases, it is suggested to introduce antiseptic agents into thestructure of the thread in order to give it better anti-infectionproperties. The antiseptic may be, e.g., myramistin (benzyldimethyl[3-(myristoylamino)propyl] ammonium chloride monohydrate),chlorhexidine, or brilliant green.

The preferable coupling agent for chitosan, hyaluronic acid and fibroinis genipin. Genipin is a chemical compound contained in gardenia fruitsextract. It is an excellent coupling agent for proteins and chitosan. Ithas the lowest toxicity among coupling agents. Genipin gives the threadsa violet color. The addition of genipin makes a thread more visible onthe operation field, therefore no need to introduce dye into the threadformula. As the thread degrades, the violet disappears. Genipin hasoutstanding anti-inflammatory properties.

The coupling agent within the thread helps retain the water inside,making the thread more elastic and allowing it to stay within thetissues for a longer time (needed for the tissue to restore), therebyallowing to control the thread's biodegradation period.

The invention is illustrated by the following examples.

For all the solutions, the weight of the polymers was calculated basedon a specific volume and concentration of the solution, considering thepolymers' humidity as well.

EXAMPLE 1

A silk surgical thread with a conditional number of 10/0 (true diameter0.020-0.029 mm) is drawn through a solution of hyaluronic acid (HAconcentration is 1.0 mass %, HA molecular weight is 1,000 kDa) and acalibrated nozzle with a diameter of 0.7 mm. Then, the thread passesthrough a thermal oven with a temperature of 100-120° C. and a 1.5 mhigh quench duct under 60-80° C. where it is dried. The forming speed is3 m per minute. The resulting mesothread has a 4 mcm thick coating madeof hyaluronic acid. The content of hyaluronic acid is 3%. The relativebreaking strength of the thread is 15 cN/tex, breaking elongation is18.0%, and elasticity modulus is 6 hPa. The resulting thread is apseudomonothread that does not have capillary canals between filamentsand is highly compatible with body tissues. The overall assessment ofthe tissue reaction is low-medium on the 15th day after the injection,and low after 4 and 6 months. The strength loss of a silk thread withcoating after being introduced into the organism takes place in 2-3months; the thread degrades completely within 4-6 months.

EXAMPLE 2

A silk surgical thread with a conditional number of 8/0 (true diameter0.040-0.049 mm) is drawn through a solution of hyaluronic acid (HAconcentration is 0.5 mass %, HA molecular weight is 1,000 kDa) and acalibrated nozzle with a diameter of 0.7 mm. Then, the thread passesthrough a thermal oven with a temperature of 100-120° C. and a 1.5 mhigh quench duct under 60-80° C. where it is dried. The forming speed is5 m per minute. The resulting thread has a 3 mcm thick coating made ofhyaluronic acid. The contents of hyaluronic acid is 2%. The relativebreaking strength of the thread is 20 cN/tex, breaking elongation is18.5%, elasticity modulus is 5.8 hPa. The resulting thread is apseudomonothread that does not have capillary canals between filamentsand is highly compatible with body tissues. The overall assessment ofthe tissue reaction is medium on the 15th day after the injection,low-medium after 4 and 6 months, and low after 8 months. The strengthloss of a silk thread with coating after being introduced into theorganism takes place in 2-3 months; the thread degrades completelywithin 10 months.

EXAMPLE 3

A silk surgical thread with a conditional number of 3/0 (true diameter0.20-0.29 mm) is drawn through a solution of hyaluronic acid (HAconcentration is 2.0 mass %, HA molecular weight is 1,000 kDa) and acalibrated nozzle with a diameter of 1.5 mm. Then, the thread passesthrough a thermal oven with a temperature of 110-130° C. and a 1.5 mhigh quench duct under 80-100° C. where it is dried. The forming speedis 2 m per minute. The resulting thread has a 15 mcm thick coating madeof hyaluronic acid. The content of hyaluronic acid is 18%. The relativebreaking strength of the thread is 33 cN/tex, breaking elongation is17.0%, and elasticity modulus is 7.1 hPa. The resulting thread is apseudomonothread that does not have capillary canals between filamentsand is highly compatible with body tissues. The overall assessment ofthe tissue reaction is low-medium on the 15th day after the injection,low after 4 and 6 months, and low after 8 months. The strength loss of asilk thread with coating after being introduced into the organism takesplace in 3-4 months; the thread degrades completely within 12 months.The thread has outstanding stress-related characteristics along withoptimum tissue reaction to its presence in the organism. EXAMPLE 4

Unlike in Example 1, the thread is drawn through a solution ofhyaluronic acid (HA concentration is 8.0 mass %, HA molecular weight is30 kDa). The resulting thread has a 73 mcm thick coating made ofhyaluronic acid. The contents of hyaluronic acid is 82%. The relativebreaking strength of the thread is 15 cN/tex, breaking elongation is15.1%, elasticity modulus is 8.4 hPa. The resulting thread is apseudomonothread that does not have capillary canals between filamentsand is highly compatible with body tissues. The overall assessment ofthe tissue reaction is low on the 15th day after the injection, and lowafter 4 months. The strength loss of a silk thread with coating afterbeing introduced into the organism takes place in 1 month; the threaddegrades completely within 5 months. A fibroin thread with a coatingfrom a concentrated HA solution with low molecular weight favors thequick vascularization of reticular connective tissue under naturalconditions without any traces of fibrosis, retaining the relativestrength of the thread. The thread has a high elasticity modulus,thereby displaying a pronounced “memory effect”. Its special feature isthat its thickness is due to a polysaccharide layer of HA which actuallycomes into contact with the body tissues.

EXAMPLE 5

Unlike in Example 4, a coupling agent is added into the forming solutionof hyaluronic acid, to-wit, the 1,4-butanediol diglycidyl ether (BDDE),and myramistin as an antiseptic. The addition of BDDE makes up 1% of theweight of hyaluronic acid, the elasticity modulus is 6.4 hPa. Theresulting thread has a HA-containing coating that is not water-solublebut can swell in water. The coating is 39 mcm thick. The contents ofhyaluronic acid is 54%. The relative breaking strength of the thread is19 cN/tex, breaking elongation is 25.5%. The resulting thread is apseudomonothread that does not have capillary canals between filamentsand is highly compatible with body tissues. The overall assessment ofthe tissue reaction is low on the 15th day after the injection, and lowafter 4 months. The strength loss of a silk thread with coating afterbeing introduced into the organism takes place in 2-3 months; the threaddegrades completely within 6-7 months. A fibroin thread with a HAcoating where the HA is chemically sealed (not water-soluble) with lowmolecular weight favors the quick vascularization of reticularconnective tissue under natural conditions without any traces offibrosis, retaining the relative strength of the thread. The threadrepresents an optimum combination of the elasticity module andelasticity when swollen. Its capacity to retain water increases itsundesirable permeability; however the presence of myramistine(antiseptic) in the formula of the thread prevents inflammations fromappearing.

EXAMPLE 6

A silk surgical thread with a conditional number of 11/0 (true diameter0.010-0.19 mm) is drawn through a solution of chitosan (chitosanconcentration is 1.0 mass %, 1.0 mass % for acetic acid) and acalibrated nozzle with a diameter of 1 mm. Then, the thread passesthrough a thermal oven with a temperature of 100-120° C. and a 1.5 mhigh quench duct under 60-80° C. where it is dried. The forming speed is3 m per minute. The thread is then drawn through a solution ofhyaluronic acid (HA concentration is 1.0 mass and a calibrated nozzlewith a diameter of 1 mm. Then, the thread passes through a thermal ovenwith a temperature of 100-120° C. and a 1.0 m high quench duct under60-80° C. where it is dried. The forming speed is 3 m per minute. Incompliance with the selected conditions and application parameters(temperatures in the oven and in the quench duct, diameter of thenozzle, forming speed, concentrations of chitosan and hyaluronic acid,viscosity of the solutions), the resulting thread has a coating from apolyelectrolytic complex of hyaluronic acid and chitosan, 18 mcm thick.The contents of the PEC of hyaluronic acid and chitosan is 10%. Therelative breaking strength of the thread is 16 cN/tex, breakingelongation is 16.0%, elasticity modulus is 6.8 hPa.

The resulting thread is a pseudomonothread that does not have capillarycanals between filaments and is highly compatible with body tissues. Theoverall assessment of the tissue reaction is low on the 2nd day afterthe injection, low on the 15th day, and low after 3 months. The strengthloss of a silk thread with coating after being introduced into theorganism takes place in 2 months; the thread degrades completely within4-5 months. A fibroin thread with coating from the PEC of hyaluronicacid and chitosan has haemostatic and antibacterial properties, favorsthe vascularization of the reticular connective tissue under naturalconditions without forming a scar.

EXAMPLE 7

Unlike in Example 6, a silk thread with a conditional number of 9/0(true diameter 0.030-0.039 mm) is used, so the resulting thread has acoating from the polyelectrolyte complex of hyaluronic acid withchitosan, 20 mcm thick. The contents of the PEC of hyaluronic acid andchitosan is 16%. The relative breaking strength of the thread is 26cN/tex, breaking elongation is 16.0%, elasticity modulus is 7.3 hPa. Theresulting thread is a pseudomonothread that does not have capillarycanals between filaments and is highly compatible with body tissues. Theoverall assessment of the tissue reaction is low-medium on the 2nd dayafter the injection, low on the 15th day, and low after 5 months. Thestrength loss of a silk thread with coating after being introduced intothe organism takes place in 5 months; the thread degrades completelywithin 7-8 months. A fibroin thread with coating from the PEC ofhyaluronic acid and chitosan has haemostatic and antibacterialproperties, favors the vascularization of the reticular connectivetissue under natural conditions without forming a scar.

EXAMPLE 8

Unlike in Example 6, a silk thread with a conditional number of 4/0(true diameter 0.15-0.19 mm) is used, so the resulting thread has acoating from the polyelectrolyte complex of hyaluronic acid withchitosan, 26 mcm thick. The overall content of PEC is 21%. The relativebreaking strength of the thread is 20 cN/tex, breaking elongation is16.5%, elasticity modulus is 7.9 hPa. The resulting thread is apseudomonothread that does not have capillary canals between filamentsand is highly compatible with body tissues. The overall assessment ofthe tissue reaction is low-medium on the 15th day after the injection,and low after 8 months. The strength loss of a silk thread with coatingafter being introduced into the organism takes place in 6 months; thethread degrades completely within 10-12 months. A fibroin thread withcoating from the PEC of hyaluronic acid and chitosan has haemostatic andantibacterial properties, favors the vascularization of the reticularconnective tissue under natural conditions without forming a scar. Thisthread stands out for its high elasticity module. After the mesothreadis introduced into a subcutaneous fold, the thread tries to expand,thereby smoothing out the facial fold.

EXAMPLE 9

Unlike in Example 6, the concentration of chitosan in the formingsolution is 2% and the concentration of hyaluronic acid in the formingsolution is 3%, so the resulting thread has a coating from thepolyelectrolyte complex of hyaluronic acid with chitosan, 20 mcm thick.The overall content of PEC is 23%. The relative breaking strength of thethread is 19 cN/tex, breaking elongation is 15.5%, elasticity modulus is9.1 hPa. The resulting thread is a pseudomonothread that does not havecapillary canals between filaments and is highly compatible with bodytissues. The overall assessment of the tissue reaction is low-medium onthe 15th day after the injection, and low after 8 months. The strengthloss of a silk thread with coating after being introduced into theorganism takes place in 4 months; the thread degrades completely within8-9 months. This thread stands out for its high elasticity module thatgives the thread a “memory effect”, and for its thickness, caused bymany polyelectrolyte layers, getting into contact with body tissues.

EXAMPLE 10

Unlike in Example 9, the forming speed is 2 m per minute and thediameter of the nozzle is 1.5 mm, so the resulting thread has a coatingfrom the polyelectrolyte complex of hyaluronic acid with chitosan, 22mcm thick. The overall content of PEC is 28%. The relative breakingstrength of the thread is 19 cN/tex, breaking elongation is 16.0%,elasticity modulus is 10.2 hPa. The resulting thread is apseudomonothread that does not have capillary canals between filamentsand is highly compatible with body tissues. The overall assessment ofthe tissue reaction is low-medium on the 15th day after the injection,and low after 8 months. The strength loss of a silk thread with coatingafter being introduced into the organism takes place in 4 month; thethread degrades completely within 8 months. This thread stands out forits high elasticity module that gives the thread a “memory effect”, andfor its thickness, caused by many polyelectrolyte layers, getting intocontact with body tissues.

EXAMPLE 11

Unlike in Example 6, the concentration of chitosan in the formingsolution is 0.5% and the concentration of hyaluronic acid in the formingsolution is 3%, and the number n of the thread's passes through formingsolutions of chitosan and hyaluronic acid is 3. The resulting thread hasa 23 mcm thick coating made of the polyelectrolytic complex ofhyaluronic acid and chitosan. The overall content of PEC is 30%. Therelative breaking strength of the thread is 21 cN/tex, breakingelongation is 14.0%, and elasticity modulus is 11.4 hPa. The resultingthread is a pseudomonothread that does not have capillary canals betweenfilaments and is highly compatible with body tissues. The overallassessment of the tissue reaction is low-medium on the 15th day afterthe injection, and low after 8 months. The strength loss of a silkthread with coating after being introduced into the organism takes placein 5 months; the thread degrades completely within 6-7 months. Thisthread stands out for its high elasticity module that gives the thread a“memory effect”, and for its thickness, caused by many polyelectrolytelayers, getting into contact with body tissues.

EXAMPLE 12

Unlike in Example 11, a plastifying agent is introduced into the formingsolutions of chitosan and hyaluronic acid, in the form of a readypolyvinyl alcohol solution. The PVA addition makes up 20% of the mass ofthe forming solution, both for chitosan and for hyaluronic acid. Theresulting thread has a 47 mcm thick coating made of the polyelectrolyticcomplex of hyaluronic acid and chitosan. The overall content of PEC is62%. The relative breaking strength of the thread is 28 cN/tex, breakingelongation is 27.0%, elasticity modulus is 6.4 hPa. The resulting threadis a pseudomonothread that does not have capillary canals betweenfilaments and is highly compatible with body tissues. The overallassessment of the tissue reaction is low on the 15th day after theinjection, and low after 10 and 14 months. The strength loss of a silkthread with coating after being introduced into the organism takes placein 6 months; the thread degrades completely within 14-16 months. Thethread stands out for its relative elasticity along with the highcontent of the covering polymer on the silk (fibroin) thread, and thesmoothness of the thread's surface means it is atraumatic.

EXAMPLE 13

Unlike in Example 11, a forming solution of hyaluronic acid with PVA isprepared separately. The concentration of hyaluronic acid is 8% and theconcentration of PVA is 0.3%. To make the HA solution, it is proposed touse HA with a molecular weight of 30 kDa and PVA with a molecular weightof 2 kDa. After 3 passages of the thread through forming solutions andthe drying area, a nozzle with a diameter of 2 mm is installed. Duringthe 4th passage, the ready thread with chitosan-hyaluronic coating isdrawn through the HA-PVA solution. The resulting thread has a 96 mcmthick coating made of the polyelectrolytic complex of hyaluronic acidand chitosan. The polymer content is 115%. The relative breakingstrength of the thread is 14 cN/tex, breaking elongation is 10.0%,elasticity modulus is 15.6 hPa. The resulting thread is apseudomonothread that does not have capillary canals between filamentsand is highly compatible with body tissues. The overall assessment ofthe tissue reaction is low-medium on the 15th day after the injection,and low after 8 months. The strength loss of a silk thread with coatingafter being introduced into the organism takes place in 8 months; thethread degrades completely within 14-15 months. This thread stands outfor its high elasticity module that gives the thread a “memory effect”,no rough surface of the thread, and for its thickness, caused bymultiple polyelectrolyte layers, getting into contact with body tissues.

EXAMPLE 14

Unlike in Example 13, a solution of chitosan lactate is made(concentration for chitosan 1.0 mass %, 2.0 mass % for lactate), and acoupling agent genipin is introduced into the forming solution ofhyaluronic acid, in the amount of 0.01% of the mass of polymer chitosan.The resulting thread has a 105 mcm thick coating made of thepolyelectrolytic complex of hyaluronic acid and chitosan lactate. Thepolymer content is 130%. The relative breaking strength of the thread is18 cN/tex, breaking elongation is 16.0%, elasticity modulus is 12.1 hPa.The resulting thread is a pseudomonothread that does not have capillarycanals between filaments and is highly compatible with body tissues. Theoverall assessment of the tissue reaction is low-medium on the 15th dayafter the injection, low-medium after 8, and low after 12 months. Thestrength loss of a silk thread with coating after being introduced intothe organism takes place in 6 months; the thread degrades completelywithin 10-12 months. This thread stands out for its moderate elasticitymodule that gives the thread a “memory effect”, no rough surface of thethread, and for its thickness, caused by multiple polyelectrolytelayers, getting into contact with body tissues, and, finally, itsincreased water retaining capacity. A therapeutic amount of lactic acid(lactate) in the formula of the thread improves blood circulation and,therefore, formation of new tissue. The addition of genipin makes athread more visible on the operation field, therefore no need tointroduce dye into the thread formula. As the thread degrades, theviolet disappears. Genipin has outstanding anti-inflammatory properties.

The maximum amount of the coating in the form of hyaluronic acid or itssalt or the polyelectrolytic complex of hyaluronic acid with chitosan orits salt may result in a weight increase of 100-130%. In this way, amesothread is obtained that is a multi-component thread with acore-coating structure.

As seen from the examples, the proposed mesothreads have the followingcharacteristics:

-   -   i. have a smooth and even surface and are therefore atraumatic;    -   ii. do not absorb the punch channel and do not stick to its        walls;    -   iii. are highly biocompatible with human body tissues;    -   iv. eliminate the risk of infiltration, allergies or haematomae;    -   v. the hydrolysis products of such threads do not accumulate in        the body, do not cause any tissue reactions and participate in        the restoration of cells and tissues.

The threads are monofilament, are not water-soluble and have a “memoryeffect”, tending to keep the initial shape of the thread. A threadalways tries to straighten. The “thread memory” effect is one of themain features of mesothreads. After the mesothread is introduced into asubcutaneous fold, the thread tries to expand, thereby smoothing out thefacial fold.

1. A multicomponent mesothread, comprising: a core and a coating,wherein the core is a fibroin thread and the coating contains hyaluronicacid or its salt or a polyelectrolyte complex of hyaluronic acid or itssalt.
 2. The multicomponent mesothread according to claim 1, wherein thehyaluronic acid salt comprises at least one of tetraalkylammonium,lithium, sodium, potassium, calcium, magnesium, barium, zinc, aluminum,copper, aurate, and hyaluronic acid hydrosalt.
 3. The multicomponentmesothread according to claim 1, wherein the coating further comprisingchitosan or its salt.
 4. The multicomponent mesothread according toclaim 3, wherein the chitosan comprises a chitosan with deacetylationdegree over 50%, and the chitosan salt comprises chitosan acetate,chitosan chloride, or chitosan lactate.
 5. The multicomponent mesothreadaccording to claim 1, wherein the core and/or coating additionallycontains a plastifying agent.
 6. The multicomponent mesothread accordingto claim 5, wherein the plastifying agent comprises polyvinyl alcohol.7. The multicomponent mesothread according to claim 1, wherein thecoating additionally contains an antiinfection agent and/or anantiseptic and/or an antibiotic.
 8. The multicomponent mesothreadaccording to claim 1, wherein the coating additionally contains anantiinfection agent, wherein the antiinfection agent comprisesbeta-(5-nitrofuril-2)-acrolein.
 9. The multicomponent mesothreadaccording to claim 1, wherein the coating additionally contains anantiseptic agent, wherein the antiseptic agent comprises benzyldimethyl[3-(myristoylamino)propyl] ammonium chloride monohydrate.
 10. Themulticomponent mesothread according to claim 1, wherein the coatingadditionally contains a coupling agent selected from the groupconsisting of ethyleneglycol diglycidyl ether, diethyleneglycoldiglycidyl ether, triethyleneglycol diglycidyl ether, polyethyleneglycoldiglycidyl ether, propyleneglycol diglycidyl ether, 1,4-butanedioldiglycidyl ether, 1,6-hexandiol diglycidyl ether.
 11. The multicomponentmesothread according to claim 1, wherein the coating additionallycontains a coupling agent, wherein the coupling agent comprises glutaricaldehyde.
 12. The multicomponent mesothread according to claim 1,wherein the coating additionally contains a coupling agent, wherein thecoupling agent comprises genipin.